This phase I/II trial studies the side effects and the best dose of lenalidomide when given together with temsirolimus and to see how well it works in treating patients with Hodgkin lymphoma or non-Hodgkin lymphoma that has come back after a period of improvement or is not responding to treatment. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of Hodgkin lymphoma or non-Hodgkin lymphoma by blocking blood flow to the cancer. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving lenalidomide together with temsirolimus may kill more cancer cells.

Patients receive lenalidomide PO on days 1-21 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 2 courses may continue therapy for up to 52 weeks.

II. To determine angiogenic and microenvironmental status of pre-treatment tissue and peripheral blood samples, and to evaluate changes following treatment with temsirolimus and lenalidomide.

III. To determine differentially expressed genes associated with differences in clinical response and in progression-free survival (PFS) in patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) (Groups A and B, respectively).

IV. To determine a methylation signature predictive of clinical response and PFS in patients with DLBCL and FL (Groups A and B, respectively).

OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II study.

Patients receive lenalidomide orally (PO) on days 1-21 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 2 courses may continue therapy for up to 52 weeks.

After completion of study treatment, patients are followed up for 1 year.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Histology: bone marrow biopsies (with the exception of lymphoplasmacytic lymphoma) as the sole means of diagnosis are not acceptable; fine needle aspirates are not acceptable

Phase I: previously treated, histologically confirmed Hodgkin and non-Hodgkin lymphomas; the only exception to a requirement for a lymph node biopsy is lymphoplasmacytic lymphoma, which can be diagnosed based on morphologic evidence in the bone marrow plus the appropriate paraprotein

All patients are required to have measurable disease; non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable; lesions that are considered non-measurable include the following:

Bone lesions (lesions if present should be noted)

Ascites

Pleural/pericardial effusion

Lymphangitis cutis/pulmonis

Bone marrow (involvement by lymphoma should be noted)

For Waldenstrom's macroglobulinemia, measurable disease is defined as at least one lesion with a single diameter of greater than 2 cm by computed tomography or bone marrow involvement with greater than 10% malignant cells and quantitative monoclonal protein (immunoglobulin M [IgM], IgG, IgA) greater than 1,000 mg/dL

Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure

Ability to understand and the willingness to sign a written informed consent document

Patients who are human immunodeficiency virus (HIV) positive are allowed to participate BUT must meet the following criteria:

No acquired immune deficiency syndrome (AIDS)-defining illness, AND

Cluster of differentiation (CD) 4 count >= 400 cells/mm^3, AND

No anti-retroviral therapy (including high-active antiretroviral therapy [HAART]) within 7 days of starting protocol therapy, AND

Patient may not take concurrent anti-retroviral therapy (including HAART) while on protocol

NOTE: it is not generally recommended to suspend anti-retroviral therapy (including HAART); the medical team enrolling a patient who suspends anti-retroviral therapy for the purpose of study participation must have a documented note reviewing the potential risks/benefits with the patient in the medical chart

Exclusion Criteria:

Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

Patients who are receiving any other investigational agents

Patients with known brain metastases should be excluded from this clinical trial

History of allergic reactions attributed to compounds of similar chemical or biological composition to temsirolimus or lenalidomide used in study

No "currently active" second malignancy, other than non-melanoma skin cancers; patients are not considered to have a "currently active" second malignancy if they have completed anti-cancer therapy and are considered by their physicians to be at less than 30% risk of relapse

No history (within 3 months of study entry) of deep venous thrombosis/pulmonary embolism (DVT/PE); patients with a distant history (greater than 3 months before study entry) of DVT/PE are eligible, but should receive prophylactic aspirin or low molecular weight heparin

No corticosteroids within 14 days prior to study, except for maintenance therapy for a non-malignant disease; maintenance therapy dose may not exceed 10 mg/day prednisone or equivalent; any patient on steroid therapy must receive thromboembolic prophylaxis

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01076543